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Short-Term ART After Early Infection Does Not Delay AIDS or Death
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6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 17-20, 2011, Rome
Mark Mascolini
Starting antiretroviral therapy (ART) within 6 months of HIV seroconversion and maintaining treatment for 12 or 48 weeks had no significant impact on rates of AIDS, serious adverse events, or death through 4 years of follow-up when compared with no treatment in the randomized SPARTAC trial [1]. The 48-week course did delay time to a CD4 count below 350, but that delay appeared to be no longer than time already spent on treatment.
Theories abound to justify starting ART immediately in people diagnosed with primary or early HIV infection, but no randomized trial has yielded evidence soundly supporting this strategy. SPARTAC, the largest randomized trial of immediate intervention versus no treatment in early infection, recruited 371 people with lab evidence of HIV infection within 6 months of a previous earlier test and randomized them to one of three arms: 48 weeks of ART, 12 weeks of ART, or no therapy (the control arm). The primary endpoint was time to a CD4 count below 350 or to starting long-term ART. There were 11 study sites in the UK, 10 in Australia, 9 in South Africa, and 1 or 2 in Brazil, Ireland, Italy, Spain, and Uganda.
Median age of the study group was 32 years (28 in Africa, 36 elsewhere), median CD4 count 559, and median viral load 4.53 log (about 35,000 copies). All participants from African sites were women, compared with only 4% from other sites; 40% overall were women. Estimated duration of infection at randomization was 12 weeks. Most people (57%) had HIV-1 subtype B infection, though 33% had subtype C, and the rest had another subtype. Twenty-one people (6%) had evidence of resistance to one or more antiretrovirals.
During a median follow-up of 4.2 years (interquartile range [IQR] 3.5 to 7.2), 13% of participants stopped returning for study visits. People randomized to the 48-week course had a 37% lower risk of reaching the primary endpoint than people in the control group (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.45 to 0.90, P = 0.01). There was no primary-endpoint difference between the 12-week course and the control arm (HR 0.93, 95% CI 0.67 to 1.29, P = 0.67). People in the 48-week arm had a 32% lower risk of reaching the primary endpoint than people in the 12-week arm (HR 0.68, 95% CI 0.48 to 0.96, P = 0.03).
SPARTAC investigators also identified a trend to delay in reaching the primary endpoint in people infected within 12 weeks of starting the 48-week course and the control group but not in those infected more than 12 weeks before starting ART.
Next the researchers compared average change in viral load from study entry to 36 weeks after ART interruption in the two intervention arms and 36 after randomization in the no-intervention control arm. Average viral load was significantly lower in the 48-week intervention arm than in the control arm (-0.44 log, 95% CI -0.64 to -0.25), and this difference persisted for 60 weeks. But there was no difference between the 12-week intervention arm and the control arm.
Whether the less than half-log difference between the 48-week group and the control group has any clinical significance is uncertain. It did not in analyses completed so far: Throughout follow-up, the three study group did not differ in rates of AIDS, serious adverse events, or death. Among the 172 study participants who began long-term ART, the groups did not differ in virologic failure rates. And CD4 gains after starting ART were similar across the three groups.
The SPARTAC team concluded that a 48-week course of ART within 6 months of infection is "associated with a significant delay in time to CD4 below 350 or long-term ART initiation, although the actual delay may not have been any longer than the time spent on treatment." At the same time, the trial yielded no evidence that interrupting early ART had a negative clinical impact.
Reference
1. Fidler S, SPARTAC Trial Investigators. The effect of short-course antiretroviral therapy in primary HIV infection: final results from an international randomised controlled trial; SPARTAC. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract WELBX06.
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